INT108919

Context Info Confidence 0.34 First Reported 2003 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 9 Total Number 10 Disease Relevance 3.55 Pain Relevance 4.74

cytosol (Mapk9) mitochondrion (Mapk9) nucleus (Mapk9) kinase activity (Mapk9) transcription factor binding (Mapk9) cytoplasm (Mapk9)

Anatomy Link Frequency liver 1 Mapk9 (Mus musculus)

Pain Link Frequency Relevance Heat Paracetamol 19 99.92 chemokine 1 99.72 Analgesic 8 99.68 opioid receptor 8 99.60 Leflunomide 10 99.52 cytokine 52 99.44 rheumatoid arthritis 95 95.56 antagonist 7 94.64 agonist 2 93.40 Opioid 11 89.64

Disease Link Frequency Relevance Heat Stress 7 100.00 Injury 7 99.70 Pathologic Processes 1 99.40 Overdose 1 99.08 Apoptosis 31 98.24 Liver Failure 1 97.00 Death 8 96.78 Rheumatoid Arthritis 95 95.56 Skin Cancer 1 94.00 Bordatella Infection 1 93.44

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

BACKGROUND INFORMATION: The MAPK (mitogen-activated protein kinase) superfamily of proteins consists of four separate signalling cascades: the c-Jun N-terminal kinase or stress-activated protein kinases (JNK/SAPK); the ERKs (extracellular-signal-regulated kinases); the ERK5 or big MAPK1; and the p38 MAPK group of protein kinases, all of which are highly conserved.

Positive_regulation (conserved) of c-Jun N-terminal kinase associated with stress

1) Confidence 0.34 Published 2005 Journal Biol. Cell Section Abstract Doc Link 15850458 Disease Relevance 0.24 Pain Relevance 0.10

Ligand-directed c-Jun N-terminal kinase activation disrupts opioid receptor signaling.

Positive_regulation (activation) of c-Jun N-terminal kinase associated with analgesic and opioid receptor

2) Confidence 0.29 Published 2010 Journal Proc. Natl. Acad. Sci. U.S.A. Section Title Doc Link 20534436 Disease Relevance 0.13 Pain Relevance 1.31

Instead, leflunomide inhibited APAP-induced activation (phosphorylation) of c-jun NH2-terminal protein kinase (JNK), thus preventing downstream Bcl-2 and Bcl-XL inactivation and protecting from mitochondrial permeabilization and cytochrome c release.

Positive_regulation (activation) of c-jun NH2-terminal protein kinase associated with paracetamol and leflunomide

3) Confidence 0.27 Published 2007 Journal Hepatology Section Abstract Doc Link 17366662 Disease Relevance 0.50 Pain Relevance 1.36

Deletion of apoptosis signal-regulating kinase 1 attenuates acetaminophen-induced liver injury by inhibiting c-Jun N-terminal kinase activation.

Positive_regulation (activation) of c-Jun N-terminal kinase in liver associated with paracetamol, injury and apoptosis

4) Confidence 0.27 Published 2008 Journal Gastroenterology Section Title Doc Link 18700144 Disease Relevance 0.58 Pain Relevance 0.47

This costimulatory signal functions through the activation of the c-Jun N-terminal kinase pathway, and it is important in lowering the threshold in response to TCR stimulation.

Positive_regulation (activation) of c-Jun N-terminal kinase

5) Confidence 0.19 Published 2003 Journal Arthritis Res Ther Section Body Doc Link PMC193735 Disease Relevance 0.22 Pain Relevance 0.06

NAC inhibits activation of c-Jun N-terminal kinase, p38 MAP kinase and redox-sensitive activating protein-1 and nuclear factor kappa B transcription factor activities regulating expression of numerous genes.

Positive_regulation (activation) of c-Jun N-terminal kinase

6) Confidence 0.11 Published 2003 Journal Cell. Mol. Life Sci. Section Abstract Doc Link 12613655 Disease Relevance 0.71 Pain Relevance 0.14

B activation and the phosphorylation and activation of the extracellular signal-regulated kinase, Jun N-terminal kinase, and p38 mitogen-activated protein kinase pathways [56].

Positive_regulation (activation) of Jun N-terminal kinase

7) Confidence 0.10 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592787 Disease Relevance 0.26 Pain Relevance 0.28

B and Jun N-terminal kinase activation using the TNF receptor adaptor proteins TRAF1, TRAF2, and TRAF6 [36-39].

Positive_regulation (activation) of Jun N-terminal kinase

8) Confidence 0.10 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592787 Disease Relevance 0.16 Pain Relevance 0.05

activation of JNK2 in response to TPA, thereby delaying AP-1

Positive_regulation (activation) of JNK2

9) Confidence 0.08 Published 2004 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC1082887 Disease Relevance 0.25 Pain Relevance 0

Death-promoting effects have been ascribed to inhibition of nuclear factor-kappaB, increase of Fas expression, p53 stabilization, cytokine and chemokine release, and activation of nitric oxide synthase, p38, and c-Jun-N-terminal kinase.

Positive_regulation (activation) of c-Jun-N-terminal kinase associated with chemokine, death and cytokine

10) Confidence 0.08 Published 2004 Journal Pharmacol. Rev. Section Abstract Doc Link 15317908 Disease Relevance 0.50 Pain Relevance 0.97

General Comments

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